These studies will explore the role of gut-associated lymphoid tissue (GALT) in the secretory immune system, whose effector arm is immunoglobulin A (IgA) plasma cells prevalent at various exocrine sites, including the respiratory tract, salivary glands, lactating mammary gland, and genitourinary tract, as well as the intestine itself. These cells synthesize the IgA which is actually or potentially the main effector of adaptive immunity to respiratory, enteric, and venereal infections, and dental carries. IgA also can act to prevent absorption of a variety of molecules from the intestinal tract, including toxins and possible carcinogens. Previous work has shown that GALT is the source of IgA-secreting plasma cells in the intestine and lactating mammary gland. Our present aim is to test the hypothesis that GALT can be induced by oral immunization to seed all the mucous membranes and exocrine tissues with IgA plasma cells synthesizing antibody of any desired specificity. We want first to develop optimal methods for stimulating GALT to confer specific immunity in the intestine and breast, second to show that specific immunity has also been conferred on other epithelial surfaces, and third to show that immunity can be transferred to immunologic virgins by transfer of cells from GALT. Specific immunity will be demonstrated by showing that a) plasma cells containing anti-hapten IgA occur in the various mucous membranes of mice immunized orally with hapten-protein conjugates and b) IgA with neutralizing activity toward influenza A virus occurs in the exocrine secretions of orally immunized mice (or recipients of passively transferred immune GALT cells), and protects their respiratory tracts from challenge. We thus hope to show that GALT can be exploited in new, simple, safe, and effective ways for disseminating secretory immunity to distant sites.